VCV001806120.1 - ClinVar

NM_001349338.3(FOXP1):c.482_483dup (p.Gln162fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001349338.3(FOXP1):c.482_483dup (p.Gln162fs)

Variation ID: 1806120 Accession: VCV001806120.1

Type and length

Duplication, 2 bp

Location

Cytogenetic: 3p13 3: 71052563-71052564 (GRCh38) [ NCBI UCSC ] 3: 71101714-71101715 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 24, 2022	Dec 24, 2022	Aug 28, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_001349338.3:c.482_483dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001336267.1:p.Gln162fs	frameshift
NM_001244808.3:c.482_483dup	NP_001231737.1:p.Gln162fs	frameshift
NM_001244810.2:c.482_483dup	NP_001231739.1:p.Gln162fs	frameshift
NM_001244812.3:c.283-5470_283-5469dup		intron variant
NM_001244813.3:c.182_183dup	NP_001231742.1:p.Gln62fs	frameshift
NM_001244814.3:c.482_483dup	NP_001231743.1:p.Gln162fs	frameshift
NM_001244815.2:c.182_183dup	NP_001231744.2:p.Gln62fs	frameshift
NM_001244816.2:c.482_483dup	NP_001231745.1:p.Gln162fs	frameshift
NM_001349337.2:c.179_180dup	NP_001336266.2:p.Gln61fs	frameshift
NM_001349339.1:c.482_483dup	NP_001336268.1:p.Gln162Asnfs	frameshift
NM_001349340.3:c.482_483dup	NP_001336269.1:p.Gln162fs	frameshift
NM_001349341.3:c.479_480dup	NP_001336270.1:p.Gln161fs	frameshift
NM_001349342.3:c.182_183dup	NP_001336271.1:p.Gln62fs	frameshift
NM_001349343.3:c.179_180dup	NP_001336272.1:p.Gln61fs	frameshift
NM_001349344.3:c.179_180dup	NP_001336273.1:p.Gln61fs	frameshift
NM_001370548.1:c.182_183dup	NP_001357477.1:p.Gln62fs	frameshift
NM_032682.6:c.482_483dup	NP_116071.2:p.Gln162fs	frameshift
NR_146142.3:n.1086_1087dup		non-coding transcript variant
NR_146143.3:n.1083_1084dup		non-coding transcript variant
NC_000003.12:g.71052564_71052565dup
NC_000003.11:g.71101715_71101716dup
NG_028243.1:g.536425_536426dup

... more HGVS ... less HGVS

Protein change

Q161fs, Q162fs, Q61fs, Q62fs

Other names

Canonical SPDI

NC_000003.12:71052563:TT:TTTT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
FOXP1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	841	920

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Intellectual disability-severe speech delay-mild dysmorphism syndrome	Pathogenic (1)	criteria provided, single submitter	Aug 28, 2019	RCV002470404.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Aug 28, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Intellectual disability-severe speech delay-mild dysmorphism syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002767805.1 First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022	Comment: A heterozygous frameshift duplication variant, NM_032682.5(FOXP1):c.482_483dup, has been identified in exon 9 of 21 of the FOXP1 gene. NB: This variant is non-coding in one … (more) A heterozygous frameshift duplication variant, NM_032682.5(FOXP1):c.482_483dup, has been identified in exon 9 of 21 of the FOXP1 gene. NB: This variant is non-coding in one alternative transcript. This duplication is predicted to create a frameshift starting at amino acid position 162, introducing a stop codon 45 residues downstream (NP_116071.2(FOXP1):p.(Gln162Asnfs*45)). This variant is predicted to result in loss of protein function through nonsense mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD) and has not been previously reported in clinical cases. However, many loss of function variants have been reported as pathogenic (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC. (less)

Comment:

A heterozygous frameshift duplication variant, NM_032682.5(FOXP1):c.482_483dup, has been identified in exon 9 of 21 of the FOXP1 gene. NB: This variant is non-coding in one alternative transcript. This duplication is predicted to create a frameshift starting at amino acid position 162, introducing a stop codon 45 residues downstream (NP_116071.2(FOXP1):p.(Gln162Asnfs*45)). This variant is predicted to result in loss of protein function through nonsense mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD) and has not been previously reported in clinical cases. However, many loss of function variants have been reported as pathogenic (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Dec 07, 2024

ClinVar Genomic variation as it relates to human health

NM_001349338.3(FOXP1):c.482_483dup (p.Gln162fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...